Karabulut Sedat, Sizochenko Natalia, Orhan Adnan, Leszczynski Jerzy
Department of Chemistry, Faculty of Science and Literature, Balikesir University, Balikesir 10145, Turkey.
Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University, Jackson, 39217-0510 MS, USA.
J Mol Graph Model. 2016 Nov;70:23-29. doi: 10.1016/j.jmgm.2016.09.005. Epub 2016 Sep 6.
Diaminopyrimidine derivatives are frequently used as inhibitors of human dihydrofolate reductase, for example in treatment of patients whose immune system are affected by human immunodeficiency virus. Forty-seven dicyclic and tricyclic potential inhibitors of human dihydrofolate reductase were analyzed using the quantitative structure-activity analysis supported by DFT-based and DRAGON-based descriptors. The developed model yielded an RMSE deviation of 1.1 a correlation coefficient of 0.81. The prediction set was characterized by R=0.60 and RMSE=3.59. Factors responsible for inhibition process were identified and discussed. The resulting model was validated via cross validation and Y-scrambling procedure. From the best model, we found several mass-related descriptors and Sanderson electronegativity-related descriptors that have the best correlations with the investigated inhibitory concentration. These descriptors reflect results from QSAR studies based on characteristics of human dihydrofolate reductase inhibitors.
二氨基嘧啶衍生物经常被用作人类二氢叶酸还原酶的抑制剂，例如用于治疗免疫系统受人类免疫缺陷病毒影响的患者。使用基于密度泛函理论（DFT）和基于DRAGON的描述符支持的定量构效分析，对47种双环和三环人类二氢叶酸还原酶潜在抑制剂进行了分析。所开发的模型产生的均方根误差（RMSE）偏差为1.1，相关系数为0.81。预测集的特征是R = 0.60和RMSE = 3.59。确定并讨论了负责抑制过程的因素。通过交叉验证和Y-打乱程序对所得模型进行了验证。从最佳模型中，我们发现了几个与质量相关的描述符和与桑德森电负性相关的描述符，它们与研究的抑制浓度具有最佳相关性。这些描述符反映了基于人类二氢叶酸还原酶抑制剂特征的定量构效关系（QSAR）研究结果。
